The object of this program project is to mount a broadly based assault in the general area of thrombotic disease. To this end a group of eight clinical and basic scientists are joining together to investigate the underlying basis of human blood coagulation and some of its intravascular consequences. Several of the proposed research projects deal with the biochemistry and physiology of blood platelets, several others with the proteins involved in blood clotting, and two others with the phenomenon of thrombogenic surfaces. Another deals with synthetic thrombolytic agents and the design and construction of latent thrombin inhibitors. In addition, a major collaborative effort has been framed which would evaluate a series of potential "early warning" procedures in hopes of diagnosing major thrombo-embolic events in advance of their occurrence. The rationale behind this program project has at least a two-fold aspect. First, the intellectual advantages of collaborative efforts by biochemists, a surgeon, an organic chemist and hematologists have already proven of benefit in terms of new ideas for solving old problems. Secondly, there are great practical advantages to the collaboration, including the exchange of many materials and services. In this regard also, CORE units have been proposed in the areas of immunology, major equipment sharing and service and radiochemistry.